We propose an R21 study to adapt the evidence-based systems analysis and improvement approach (SAIA) intervention and apply it to the delivery of overdose education and naloxone distribution (OEND) programs in the United States. The age-adjusted opioid overdose mortality rate rose nearly 250% from 2000 to 2015, indicating that the opioid overdose epidemic continues to surge in the United States. Opioid overdose mortality is preventable with the administration of naloxone, an opioid antagonist, during an overdose event. OEND programs train laypersons?people who use drugs, family members, peers?as prospective responders in overdose events by providing access to naloxone and training for its delivery. A recent meta-analysis demonstrated that OEND programs were highly effective at preventing opioid overdose mortality, especially when they reach high levels of coverage. Despite their effectiveness, a national study by the proposed investigators recently showed that OEND programs had not reached sufficient coverage to reduce opioid overdose mortality at the national level. Methadone maintenance treatment and syringe service programs have implemented OEND programs, as the large majority of their clients are potential opioid overdose bystanders. To reduce opioid overdose mortality, OEND programs must engage potential opioid overdose bystanders in a series of steps over time, including training in overdose reversal, receiving naloxone, obtaining refills of naloxone when needed, possessing naloxone, using naloxone during observed overdoses, and obtaining refills once they no longer have naloxone. We refer to this series of steps as the naloxone delivery cascade. The SAIA intervention has demonstrated effectiveness in improving the prevention of mother-to-child transmission of HIV care cascade and is a flexible platform that can be applied to other health delivery systems, such as OEND programs. Aim 1 is to adapt the SAIA intervention to be applicable to the naloxone delivery cascade. Aim 2 is to pilot the modified SAIA intervention within overdose education and naloxone distribution programs. To achieve Aim 1, we will hold four focus group discussions with staff from four OEND programs to gather input on adapting the SAIA intervention's data collection tools. Next, we will test the tools in the four OEND programs and solicit further input to refine the tools via 4 focus group discussions and 20 semi-structured interviews. In Aim 2, we will pilot all steps of the modified SAIA intervention at the four OEND programs for 6 months. We will assess the implementation process via 20 semi-structured interviews, 4 focus group discussions, and naloxone delivery cascade improvements. The proposed study is a novel application of an evidence-based, systems-focused intervention to the naloxone delivery cascade. If adapted appropriately and found to be effective in a future R01 trial, the SAIA intervention could be scaled to a diversity of OEND programs. If successful, these efforts can optimize OEND program delivery, thereby improving our nation's response to the opioid overdose epidemic.